The present invention relates to novel processes for producing 3-thia substituted alkane 1,4-diones.
Artifical flavoring agents for foodstuffs have received increasing attention in recent years. In many areas, such food flavoring agents are preferred over natural flavoring agents at least in part because of the uniform flavor that may be so obtained. For example, natural food flavoring agents such as extracts, essences, concentrates and the like are often subject to wide variation due to changes in the quality, type and treatment of the raw materials. Such variation can be reflected in the end product and results in unreliable flavor characteristics and uncertainity as to consumer acceptance and cost. Additionally, the presence of the natural product in the ultimate food may be undesirable because of increased tendency to spoil. This is particularly troublesome in convenience and snack food usage where such products as dips, soups, chips, prepared dinners, canned foods, sauces, gravies and the like are apt to be stored by the consumer for some time prior to use.
The fundamental problem in preparing artificial flavoring agents is that of achieving as nearly as possible a true flavor reproduction. This generally proves to be a difficult task since the magnetism for flavor development in many foods is not understood. This is noteable in products having meaty and roasted flavor characteristics. It is also noteable in products having vegetable-like and hydrolyzed vegetable protein-like and anise-like flavor characteristics.
Reproduction of roasted and meat flavors and aromas and vegetable-like and hydrolyzed vegetable protein-like and anise-like flavors and aromas has been the subject of the long and continuing search by those engaged in the production of foodstuffs. The severe shortage of foods, especially protein foods, in many parts of the world has given rise to the need for utilizing non-meat sources of proteins and making such proteins as palatable and as meatlike as possible. Hence, materials which will closely simulate or exactly reproduce the flavor and aroma of roasted meat products and liver products and vegetable products are required.
Moreover, there are a great many meat containing or meat based foods presently distributed in a preserved form. Examples being condensed soups, dry-soup mixes, dry meat, freeze-dried or lyophilized meats, packaged gravies and the like. While these products contain meat or meat extracts, the fragrance, taste and other organoleptic factors are very often impaired by the processing operation and it is desirable to supplement or enhance the flavors of these preserved foods with versatile materials which have either roasted meat or gravy-like or vegetable-like or meat-like or ham-like nuances.
2-Alkylfuran-3-thiols and bis (alkyl-3-furyl) disulfides are disclosed in U.S. Pat. No. 3,723,475 issued on Mar. 27, 1973 to supply meaty flavor aroma and taste nuances to foodstuffs. 2- thia substituted-1,4-diones are disclosed in U.S. Pat. No. 3,836,563 issued on Sept. 17, 1974 to also supply meaty flavors to foodstuffs.
Swiss Pat. No. 531,313 discloses the addition of hydrogen sulfide across a double bond, eliminating the double bond.
Such a reaction, however, is not shown in conjunction with a chemical compound which has two ketone moieties.
The mechanism of the addition of hydrogen sulfide across a double bond of an alpha-beta-unsaturated ketone is set forth at lines 40-67 of columns 3 and 4 of Swiss Pat. No. 531,559. The formation of thio esters using thio acetic acid and unsaturated ketones is set forth at lines 15-20 of column 6 of Swiss Pat. No. 531,559.
U.S. Pat. No. 2,630,452 to Crouch, et al discloses processes for reacting unsaturated nitriles with thio acids whereby the thio ester moiety adds to the double bond at the "alpha" position with respect to the CN moiety using an aqueous alkali metal hydroxide catalyst or a quaternary ammonium compound catalyst. The substance of Crouch, et al may be illustrated by the following reaction betweeen acrylonitrile and thioacetic acid: ##EQU1## At column 2, lines 40-45, Crouch, et al states:
"In accomplishing the thioacetic acidacrylonitrile reaction, it has been found to be highly advantageous to employ certain basic catalysts as reaction promoters and directors. The preferred catalyst is a quaternary ammonium compound designated by the general formula . . . "
In Example IV of Crouch, et al, acrylonitrile is reacted with thioacetic acid in the presence of a t-butyl hydroperoxide catalyst at a temperature of 43.degree.-49.degree.C.
U.S. Pat. No. 3,441,589 to Oswald discloses reaction of thiol compounds such as mercaptans and thiolcarboxylic acids being selectively added to esters which, in turn, are formed by the reaction of maleic acid, fumaric acid or maleic anhydride with terminally unsaturated alcohols such as allyl alcohol at either of the terminal double bonds of the ester functionality or at the maleic or fumaric side of unsaturation with the use of either free radical or ionic catalysts. At column 7, Example 8, Oswald teaches the reaction of diallyl maleate with thiolacetic acid to form n-(3-acetylthio)-propyl allyl maleate according to the following reaction: ##SPC3##
in the presence of a free radical catalyst, such as ultraviolet or gamma radiation or a "wide variety of peroxidic and azo compounds" (see column 3, lines 60-62).
Reid "Organic Chemistry of Bivalent Sulfur", Volume IV, 1962, Chemical Publishing Co., Inc.; discloses reactions of thioacetic acid with unsaturated compounds. At pages 15 and 16 Reid states:
"The most interesting reaction of thioacetic acid is its ready addition to unsaturates. An example of this is its addition to acrylonitrile. In this it exhibits its mercaptan character but in activity it far surpasses most mercaptans. Usually the addition takes place spontaneously and completely. With styrene the reaction is: ##SPC4##
The product is the beta-phenethyl ester of thioacetic acid and is identical with that from phenethyl mercaptan and acetyl chloride . . . "
No teaching exists in the prior art to show that where R.sub.2 is lower alkyl and R.sub.1 is hydrogen, the effect of carrying out a reaction of a 2-ene-4-one-1-al with a thioacid (in the presence of base) is directive leading substantially to a reaction product where the thioester substitution is alpha to the ketone moiety and not the aldehyde moiety.
Furthermore, given the 2-ene-1,4-dione reactants of our invention, there is no prediction in the prior art that either (i) no catalyst is necessary in the case of using a hex-3-ene-2,5-dione reactant, or (ii) a basic catalyst is needed and the addition is directive in the case of using a pent-2-ene-4-one-1-al.
The processes of the present invention provide straightforward methods for producing 3-thia substituted alkane 1,4 diones in good yields in an economical manner.
Briefly, the processes of our invention comprise the steps of:
i. Providing a 2-ene-alkane 1,4 dione having the structure: ##SPC5## PA1 ii. Intimately admixing said 2-ene-alkane-1,4 dione with a sulfur compound having the formula: EQU R.sub.3 SH PA1 thereby providing a substituted or unsubstituted 2-thia substituted 1,4 dione having the structure: ##SPC6## PA1 R.sub.3 is selected from the group consisting of acyl and aroyl, wherein R.sub.2 is lower alkyl; and wherein R.sub.1, R.sub.4 and R.sub.6 are the same or different and are each selected from the group consisting of hydrogen and lower alkyl; wherein when R.sub.1 is hydrogen, the reaction is carried out in the presence of an organic base; and wherein when R.sub.1 is lower alkyl, the reaction is carried out in the absence of catalyst. PA1 thioacetic acid PA1 thiopropionic acid PA1 thiobutyric acid PA1 thioisobutyric acid PA1 thio-n-pentenoic acid PA1 thiocinnamic acid PA1 thiobenzoic acid PA1 2-methyl-thiobenzoic acid PA1 3-methyl-thiobenzoic acid PA1 4-methyl-thiobenzoic acid PA1 2,4-dimethyl-thiobenzoic acid PA1 3,5-dimethyl-thiobenzoic acid PA1 Methyl thiazole alcohol (4-methyl-5-betahydroxyethyl thiazole); PA1 2-Methyl butanethiol; PA1 4-Mercapto-2-butanone; PA1 3-Mercapto-4-pentanone; PA1 1-Mercapto-2-propanone; PA1 Benzaldehyde; PA1 Furfural; PA1 Furfural alcohol; PA1 2-Mercapto propionic acid; PA1 2-Pentene; PA1 Alkyl pyrazine; PA1 Methyl pyrazine; PA1 2-Ethyl-3-methyl pyrazine; PA1 Tetramethyl pyrazine; PA1 Polysulfides; PA1 Dipropyl disulfide; PA1 Methyl benzyl disulfide; PA1 Alkyl thiophenes; PA1 2-Butyl thiophene; PA1 2,3-Dimethyl thiophene; PA1 5-Methyl furfural; PA1 Acetyl furan; PA1 2,4-Decadienal; PA1 Guiacol; PA1 Phenyl acetaldehyde; PA1 .delta.-Decalactone; PA1 d-Limonene; PA1 Acetoin; PA1 Amyl acetate; PA1 Maltol; PA1 Ethyl butyrate; PA1 Levulinic acid; PA1 Piperonal; PA1 Ethyl acetate; PA1 n-Octanal; PA1 n-Pentanal; PA1 Hexanal; PA1 Diacetyl; PA1 Monosodium glutamate; PA1 Sulfur-containing amino acids; PA1 Cysteine; PA1 Hydrolyzed vegetable protein; PA1 Hydrolyzed fish protein; and PA1 Tetramethyl pyrazine
wherein
Two particularly novel features of our invention involve (i) addition of the thiol acids, either ##EQU2## or ##EQU3## to a hex-3-ene-2,5-dione, e.g., having the structure: ##SPC7##
at room temperature in the absence of any catalyst to produce economic yields of 3-thia substituted alkane 1,4 dione, e.g., having the structure: ##SPC8##
and (ii) addition of a thiol acid, either ##EQU4## or ##EQU5## to pent-3-ene-4-one-1-als, e.g., having the structure: ##SPC9##
in the presence of an organic base to yield a 3-thia substituted pentane-4-one-1-al, e.g., having the structure: ##SPC10##
the addition being directive to that carbon atom (originally having the C=C double bond) which is "alpha" to the carbonyl group of the ketone moiety rather than the aldehyde moiety.
Examples of thio acids useful in our process are:
Whether an organic base is used or not in the reaction with the 2-ene-1,4 dione with the thio acid having the formula R.sub.3 SH, the 2-ene-1,4 dione can be exemplified as follows: Compound R.sub.1 R.sub.2 R.sub.4 Name ______________________________________ 3-Hexen-2,5-dione Methyl Methyl Hydrogen 3-Methyl-3-hexen- Methyl Methyl Methyl 2,5 dione 3-Methyl-3-hepten- Methyl Ethyl Methyl 2,5 dione 3-Ethyl-3-hepten- Methyl Ethyl Ethyl 2,5-dione 4-Ethyl-4-octen- Ethyl Ethyl Ethyl 3,6 dione 3-Propyl-3-hepten- Methyl Ethyl Propyl 2,5 dione 4-Methyl-3-hepten- Ethyl Methyl Methyl 2,5 dione 4-Methyl-4-octen- Ethyl Ethyl Methyl 3,6-dione 4-Methyl-4-nonen- Ethyl Propyl Methyl 3,6-dione 4-Propyl-3-hepten- Ethyl Methyl Propyl 3,6-dione 5-Methyl-5-decen- Propyl Propyl Methyl 4,7-dione 5-Methyl-4-nonen- Propyl Ethyl Methyl 3,6-dione 4-Methyl-3-nonen- Butyl Methyl Methyl 2,5-dione 4-Ethyl-3-nonen- Butyl Methyl Ethyl 2,5-dione 3-Methyl-3-nonen- Methyl Butyl Methyl 2,5-dione 3-Propyl-3-nonen- Methyl Butyl Propyl 2,5 dione 3-Butyl-3-hexen- Methyl Methyl Butyl 2,5-dione 4-Octen-3,6-dione Ethyl Ethyl Hydrogen ______________________________________
As stated above, R.sub.1 and R.sub.2 can each be hydrogen for the purposes of these processes of our invention in the event that in the reaction of the 2-ene-1,4 dione with the thioacid of the formula R.sub.3 SH, an organic base is used. Hence, in addition to the foregoing compounds, the following compounds can be utilized in the reaction with R.sub.3 SH:
Compound R.sub.1 R.sub.2 R.sub.4 Name ______________________________________ 2-Buten-1,4-dial Hydrogen Hydrogen Hydrogen 2-Methyl-2-buten- Hydrogen Hydrogen Methyl 1,4-dial 2-Pentenal-4-one Methyl Hydrogen Hydrogen 2-Hexenal-4-one Ethyl Hydrogen Hydrogen 3-Methyl-2-hexenal Ethyl Hydrogen Methyl 4-one 2-Methyl-2-pentenal Hydrogen Hydrogen Methyl 4-one 2-Methyl-2-heptenal Hydrogen Propyl Methyl 4-one 2-Methyl-2-octenal Hydrogen Butyl Methyl 4-one ______________________________________
Examples of useful organic bases are piperidine, pyridine, quinoline, triethyl amine and alpha-picoline.
The reaction may be carried out in a solvent such as water or an ether such as diethyl ether or a hydrocarbon such as benzene or hexane or cyclohexane. The reaction may also be carried out without the use of a solvent. The reaction may be carried out under reflux conditions although temperatures varying from 0.degree. up to 60.degree.C are suitable and will give rise to commercially suitable yields. When the reaction is carried out with highly volatile reactants, higher pressures than atmospheric pressure are preferred, e.g., three atmospheres pressure. Examples of reaction products, 3-thia-substituted-1,4-diones which are formed from the reaction of the 2-ene-1,4-diones with the thioacids, having the formula R.sub.3 SH are as follows:
3-Thia Substituted 2-ene-1,4 dione R.sub.3 SH 1,4-dione Reaction Reactant Reactant Product ______________________________________ 3-Hexen-2,5-dione Thioacetic acid 3-Thioacetyl- 2,5-hexan-dione 3-Methyl-3-hexen- Thiopropionic 3-Thiopropionyl-4- 2,5-dione acid methyl hexan-2,5- dione 3-Methyl-3-hepten- Thiobenzoic acid 4-Thiobenzoyl-4- 2,5-dione methyl heptan-3,6- dione 4-Ethyl-4-octen- Thioacetic acid 4-Thioacetyl-5- 3,6-dione ethyl-octan-3,6- dione 2-Buten-1,4-dial Thioacetic acid 2-Thioacetyl-butan- 1,4-dial 2-Pentenal-4-one 4-Methyl-thio 3-Thiobenzoyl- benzoic acid pentenal-4-one 2-Pentenal-4-one Thioacetic acid 3-Thioacetyl- pentenal-4-one ______________________________________
The 2-thia substituted-1,4-diones as exemplified above are useful for altering the organoleptic properties of consumable materials, more particularly, foodstuffs. Thus, for example, 3-thioacetyl-2,5-hexanedione has a roasted meat aroma and a pot-roast and roasted meat flavor tested at levels of 5 ppm. Its flavor threshold value is at 1 ppm. The compound 3-thiobenzoyl-2,5-hexanedione has a berry and a meat aroma, an allium, earthy and horseradish flavor at concentrations of approximately 0.5 ppm. Its threshold value is at 0.5 ppm. 3-Thiobenzoyl-2,5-hexanedione at 5 ppm evaluated in beef bouillon has a meaty note. 3-Thioacetyl-2,5-hexanedione at 5 ppm adds a burnt meat note to beef bouillon. 3-Thiobenzoyl-2,5-hexanedione adds a slight green chicken meat note to chicken broth at 2.5 ppm. 3-Thioacetyl-2,5-hexanedione adds eggy chicken notes to chicken broth at 2.5 ppm.
The products of the process of our invention may be used as reaction intermediates and, when used as such, the thia-substituted 1,4-diones produced by the process of our invention are then cyclized to form substituted or unsubstituted 3-thiafurans according to the following reaction: ##SPC11##
wherein R.sub.1 and R.sub.2 are the same or different and are each hydrogen or lower alkyl; wherein R.sub.3 is either acyl or aroyl and R.sub.4 is hydrogen or lower alkyl. The resulting 3-thiafurans may be used as such for their organoleptic properties or they may be hydrolyzed and then reacylated or aroylated to form other acyl thia or aroyl thia substituted furans which have still other organoleptic properties useful for flavoring foodstuffs.
The compound having the structure: ##SPC12##
may also be intermediates in that they may be hydrolyzed first using a weak base (e.g., 2-5% aqueous NaOH, LiOH or KOH) and then neutralizing with acid to a pH of 5-6 to form compounds having the structure: ##SPC13##
which have useful organoleptic properties. Thus, for example, 3-thioacetyl-2,5-hexanedione is hydrolyzed to 3-mercapto-2,5-hexanedione by treating the 3-thioacetyl compound first with 2% aqueous NaOH and then adjusting the pH to about 5 using 10% HCl. Hydrolysis conditions are preferably atmospheric pressure and 20.degree.-50.degree.C with ambient temperature being most convenient and economical.
The 3-thia alkane-1,4 dione derivatives and mixtures thereof produced according to the present invention can be used to alter, vary, fortify, modify, enhance, or otherwise improve the organoleptic properties, including flavor and/or aroma of a wide variety of materials which are ingested, consumed, or otherwise organoleptically sensed. The term "alter" in its various forms will be understood herein to mean the supplying or imparting a flavor character or note to an otherwise bland, relatively tasteless substance, or augmenting an existing flavor characteristic where the natural flavor is deficient in some regard, or supplementing the existing flavor or aroma impression to modify the organoleptic character. The materials which are so altered are generally referred to herein as consumable materials.
Such 3-thia alkane-1,4-dione derivatives are accordingly useful in flavoring compositions. Flavoring compositions are herein taken to mean those which contribute a part of the overall flavor impression by supplementing or fortifying a natural or artificial flavor in a material, as well as those which supply substantially all the flavor and/or aroma character to a consumable article.
The term "foodstuff" as used herein includes both solid and liquid ingestible materials for man or animals, which materials usually do, but need not, have nutritional value. Thus, foodstuffs includes meats, gravies, soups, convenience foods, malt and other alcoholic or non-alcoholic beverages, milk and dairy products, nut butters such as peanut butter and other spreads, seafoods, including fish, crustaceans, mollusks, and the like, candies, breakfast foods, baked goods, vegetables, cereals, soft drinks, snack foods, dog and cat foods, other veterinary products, and the like.
When the 3-thia alkane-1,4 dione derivatives produced according to the process of this invention are used in a food flavoring composition, they can be combined with conventional flavoring materials or adjuvants. Such co-ingredients or flavoring adjuvants are well known in the art for such use and have been extensively described in the literature. Apart from the requirement that any such adjuvant material be ingestibly acceptable, and thus non-toxic or otherwise non-deleterious, conventional materials can be used and broadly include other flavor materials, vehicles, stabilizers, thickeners, surface active agents, conditioners, and flavor intensifiers.
Examples of preferred co-flavoring adjuvants are:
The 3-thia alkane-1,4 dione derivatives, or the compositions incorporating them, as mentioned above, can be combined with one or more vehicles, or carriers for adding them to the particular product. Vehicles can be edible or otherwise suitable materials such as ethyl alcohol, propylene glycol, water, and the like. Carriers include materials such as gum arabic, carrageenan, other gums, and the like. The 3-thia alkane-1,4 dione compounds according to this invention can be incorporated with the carriers by conventional means such as spray-drying, drum-drying, and the like. Such carriers can also include materials for coacervating the 3-thia alkane-1,4 dione derivatives (and other flavoring ingredients, as present) to provide encapsulated products. When the carrier is an emulsion, the flavoring composition can also contain emulsifiers such as mono- and diglycerides of fatty acids and the like. With these carriers or vehicles, the desired physical form of the composition can be prepared.
The quantity of 3-thia alkane-1,4 dione derivatives or mixtures thereof utilized should be sufficient to impart the desired flavor characteristic to the product, but on the other hand, the use of an excessive amount of the derivative is not only wasteful and uneconomical, but in some instances too large a quantity may unbalance the flavor or other organoleptic properties of the product comsumed. The quantity used will vary depending upon the ultimate foodstuff; the amount and type of flavor initially present in the foodstuff; the further process of treatment steps to which the foodstuff will be subjected; regional and other preference factors; the type of storage, if any, to which the product will be subjected, and the preconsumption treatment, such as baking, frying, and so on, given to the product by the ultimate consumer. Accordingly, the terminology "effective amount" and "sufficient amount" is understood in the context of the present invention to be quantitiatively adequate to alter the flavor of the foodstuff.
It is accordingly preferred that the ultimate compositions contain from about 0.02 parts per million (ppm) to about 250 ppm of 3-thia-alkane-1,4 dione derivative or derivatives. More particularly, in food compositions it is desirable to use from 0.05 ppm to 100 ppm for enhancing flavors and in certain preferred embodiments of the invention, from about 0.2 to 50 ppm of the derivatives are included to add positive flavors to the finished product. All parts, proportions, percentages, and ratios herein are by weight unless otherwise indicated.
The amount of 3-thia alkane-1,4 dione material or materials of our invention to be utilized in flavoring compositions can be varied over a wide range depending upon the particular quality to be added to the foodstuff. Thus, amounts of one or more derivatives according to the present invention of from about 2 ppm up to 80 or 90 percent of the total flavoring composition can be incorporated in such compositions. It is generally found to be desirable to include from about 10 ppm up to about 0.1 percent of the 3-thia alkane-1,4 dione derivatives in such compositions.
The following examples I, II, V, VI, VII and X are given to illustrate embodiments of the invention as it is preferably preferred to practice it. Examples III, IV, VIII and IX are given to illustrate the usefulness of the products produced by the process of our invention. It will be understood that these examples are illustrative and the invention is not to be considered as restricted thereto except as indicated in the appended claims.